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Study in mice raises hopes for birth control pill for men

U.S. researchers have stumbled on a compound that may finally lead to a birth control pill for men.

By Julie SteenhuysenReuters

Thu., Aug. 16, 2012

CHICAGO- U.S. researchers have stumbled on a compound that may finally lead to a birth control pill for men.

In lab experiments, male mice given the pill were rendered completely infertile during treatment as they produced fewer and less mobile sperm. The drug, originally tested as part of a broader cancer research project, does not affect the hormone system or sex drive, the team said on Thursday.

“There is no effect on the mouse’s mojo. The animals exhibit the normal sexual behaviors and frequency of copulation,” said Dr. James Bradner of the Dana-Farber Cancer Institute in Boston, whose study appears in the journal Cell.

What’s more, the effect is completely reversible. Once doctors stopped giving the drug to mice, they were able to sire healthy litters, with no apparent side effects, Bradner said.

Scientists say the research is exciting because it applies a unique approach to the problem of male contraception, which is now largely comprised of less reliable methods like condom use, or more permanent procedures like vasectomies.

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Bradner’s lab focuses on developing new drugs to undermine the molecular memory of cancer cells that tell them to divide. Those memory markers are distributed throughout the genome, the DNA that makes up a person’s genetic code, and Bradner likens them to post-it notes that give cells instructions.

The team was experimenting with a compound developed in Bradner’s lab called JQ1, which was originally synthesized at Dana-Farber to block BRD4, a cancer-causing gene.

They discovered that it appears to target a protein specific to the testes called BRDT that instructs sperm to mature. Bradner said the compound does not appear to do damage to sperm-making cells, but they forget how to create mature sperm while under the influence of the drug.

Bradner reached out to reproductive health expert Martin Matzuk of Baylor College of Medicine, another author of the report, and his team tested the compound in mice.

What they found is that the animals began producing fewer sperm, and the ones they did produce were poor swimmers.

“When the drug is removed, these instructions return,” Bradner said.

The finding was surprising because few drugs are able to cross a protective firewall known as the blood-testes barrier that protects the testicles from substances floating around in the blood stream.

William Bremner from the University of Washington in Seattle, who was not involved in the research, said in a commentary the finding was “a breakthrough new approach,” noting that there has not been a new reversible contraceptive for men since the development of the condom centuries ago.

“It’s exciting basic science that provides a new approach to think about how a contraceptive for men might be designed,” Bremner said in a telephone interview. “At the same time, it’s a long ways from being in clinical trials in men, let alone being on pharmacy shelves.”

Other teams have developed hormonal pills that are effective, but they disrupt hormone balance in men, and drug companies so far have not picked up on this approach, Bremner said.

Professor Moira O’Bryan, head of the Male Infertility and Germ Cell Biology Laboratory at Monash University in Australia, said the study was “an exciting report that could have major scientific and social impacts.”

O’Bryan said the strong similarity between sperm production in mice and humans suggest that a variation of the drug may ultimately result in a human contraception for men.

Bradner said his team is working to refine the drug so that it only acts on cells in the testes, and not on cancer cells.

And while there are many more tests ahead before it can be a drug, the researchers believe the new approach can be “completely translated to men, providing a novel and efficacious strategy for a male contraceptive.”

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